Ebook Epidemiology, evidence-based medicine and public health (6/E): Part 2

Part 2 book “Epidemiology, evidence-based medicine and public health” has contents: Systematic reviews and meta-analysis, health economics, public health, infectious disease epidemiology and surveillance, health improvement, health care targets, global health, infectious disease epidemiology and surveillance,… and other contents.

In this chapter you will learn to:

✓ define a systematic review, and explain why it provides more reliable evidence than a traditional narrative review;

✓ succinctly describe the steps in conducting a systematic review;

✓ understand the concept of meta-analysis and other means of synthesising results;

✓ explain what is meant by heterogeneity;

✓ critically appraise the conduct of a systematic review.

What are systematic

reviews and why do we

need them?

Systematic reviews arestudies of studiesthat offer

a systematic approach to reviewing and

sum-marising evidence They follow a defined structure

to identify, evaluate and summarise all available

evidence addressing a particular research

ques-tion Systematic reviews should use and report

clearly-defined methods, in order to avoid the

biases associated with, and subjective nature of,

traditional narrative reviews Key characteristics of

a systematic review include a set of objectives with

pre-defined inclusion criteria, explicit and ducible methodology, comprehensive searchesthat aim to identify all relevant studies, assessment

repro-of the quality repro-of included studies, and a ised presentation and synthesis of the characteris-tics and findings of the included studies

standard-Systematic reviews are an essential tool to allowindividuals and policy makers to make evidence-based decisions and to inform the development

of clinical guidelines Systematic reviews fulfilthe following key roles: (1) allow researchers tokeep up to date with the constantly expandingnumber of primary studies; (2) critically appraiseprimary studies addressing the same researchquestion, and investigate possible reasons forconflicting results among them; (3) providemore precise and reliable effect estimates than is

Epidemiology, Evidence-based Medicine and Public Health Lecture Notes, Sixth Edition Yoav Ben-Shlomo, Sara T Brookes and Matthew Hickman.



Systematic reviews and meta-analysis 103

possible from individual studies, which are

of-ten underpowered; and (4) identify gaps in the

evidence base

How do we conduct a

systematic review?

It is essential to first produce a detailed protocol

which clearly states the review question and the

proposed methods and criteria for identifying and

selecting relevant studies, extracting data,

assess-ing study quality, and analysassess-ing results To

min-imise bias and errors in the review process, the

ref-erence screening, inclusion assessment, data

ex-traction and quality assessment should involve at

least two independent reviewers If it is not

practi-cal for all tasks to be conducted in duplicate, it can

be acceptable for one reviewer to conduct each

stage of the review while a second reviewer checks

their decisions The steps involved in a systematic

review are similar to any other research

Screen titles and abstracts

Retrieve full text papers

Apply inclusion criteria

Extract data and assess study quality

Define the review question and inclusion criteria

A detailed review question supported by clearly

de-fined inclusion criteria is an essential component

of any review For a review of an intervention theinclusion criteria should be defined in terms ofpatients, intervention, comparator interventions,outcomes (PICO) and study design Other types ofreview (for example, reviews of diagnostic test ac-curacy studies) will use different criteria

Example: We will use a review by Lawlor and

Hopker (2001) on the effectiveness of exercise as anintervention for depression to illustrate the steps

in a systematic review This review aimed ‘to mine the effectiveness of exercise as an interven-tion in the management of depression’

deter-Inclusion criteria were defined as follows:

Patients: Adults (age> 18 years) with a

diagnosis of depression (anymeasure and any severity)

Intervention: Exercise

Comparator: Established treatment of

depression Studies with anexercise control group wereexcluded

Studies reporting only anxiety

or other disorders wereexcluded

Study design: Randomised controlled trials

Identify relevant studies

A comprehensive search should be undertaken

to locate all relevant published and unpublishedstudies Electronic databases such as MEDLINEand EMBASE form the main source of publishedstudies These bibliographic databases index ar-ticles published in a wide range of journals andcan be searched online Other available databaseshave specific focuses: the exact databases, andnumber of databases, that should be searched

is dependent upon the review question TheCochrane CENTRAL register of controlled trials,which includes over 640,000 records, is the bestsingle source for identifying reports of controlledtrials (both published and unpublished) A de-tailed search strategy, using synonyms for the type

of patients and interventions of interest, and bined using logical AND and OR operators should

com-be used to help identify relevant studies

There is a trade-off between maximising the

number of relevant studies identified by the

searches whilst limiting the number of ineligible

studies in order that the search retrieves a

man-ageable number of references to screen It is

com-mon to have to screen several thousands of

refer-ences Searches of bibliographic databases alone

tend to miss relevant studies, especially

unpub-lished studies, and so additional steps should be

taken to ensure that all relevant studies are

cluded in the review For example, these could

in-clude searching relevant conference proceedings,

grey literature databases, internet websites,

hand-searching journals, contacting experts in the field,

screening the bibliographies of review articles and

included studies, and searches for citations to key

papers in the field Online trial registers are of

increasing importance in helping identify studies

that have not, or not yet, been published Search

results should be stored in a single place, ideally

using bibliographic software (such as Reference

Manager or EndNote)

Selecting studies for inclusion is a two-stage

process First, the search results, which generally

include titles and abstracts, are screened to

iden-tify potentially relevant studies The full text of

these studies is then obtained (downloaded

on-line, ordered from a library, or copy requested from

the authors) and assessed for inclusion against

the pre-specified criteria Retrieved papers are

then assessed for eligibility against pre-specified

criteria

Example: The Lawlor and Hopker (2001) review

conducted a comprehensive search including

Med-line, Embase, Sports Discus, PsycLIT, Cochrane

CENTRAL, and the Cochrane Database of

System-atic Reviews Search terms included ‘exercise,

phys-ical activity, physphys-ical fitness, walking, jogging,

run-ning, cycling, swimming, depression, depressive

disorder, and dysthymia.’ Additional steps to locate

relevant studies included screening bibliographies,

contacting experts in the field, and handsearching

issues of relevant journals for studies published in

1999 No language or publication restrictions were

applied Three reviewers independently reviewed

titles and available abstracts to retrieve potentially

relevant studies; studies needed to be identified by

only one person to be retrieved

Extract relevant data

Data should be extracted using a standardised

form designed specifically for the review, in order

to ensure that data are extracted consistentlyacross different studies Data extraction formsshould be piloted, and revised if necessary Elec-tronic data collection forms and web-based formshave a number of advantages, including thecombination of data extraction and data entry

in one step, more structured data extraction andincreased speed, and the automatic detection

of inconsistencies between data recorded bydifferent observers

Example: For the Lawlor and Hopker (2001) review

two reviewers independently extracted data on ticipant details, intervention details, trial quality,outcome measures, baseline and post interventionresults and main conclusions Discrepancies wereresolved by referring to the original papers andthrough discussion

par-Assess the quality of the included studies

Assessment of study quality is an important ponent of a systematic review It is useful to dis-tinguish between the risk of bias (internal valid-ity) and the applicability (external validity, or gen-eralisability) of the included studies to the re-view question Bias occurs if the results of a studyare distorted by flaws in its design or conduct(see Chapter 3), while applicability may be limited

com-by differences between included patients’ graphic or clinical features, or in how the interven-tion was applied, compared to the patients or in-tervention that are specified in the review ques-tion Biases can vary in magnitude: from smallcompared with the estimated intervention effect

demo-to substantial, so that an apparent finding may

be entirely due to bias The effect of a particularsource of bias may vary in direction between trials:for example lack of blinding may lead to underes-timation of the intervention effect in one study butoverestimation in another study

The approach that should be used to assessstudy quality within a review depends on the de-sign of the included studies – a large number ofdifferent scales and checklists are available Com-monly used tools include the Cochrane Risk of Biastool for RCTs and the QUADAS-2 tool for diag-nostic accuracy studies Authors often wish to usesummary ‘quality scores’ based on adding pointsthat are assigned based on a number of aspects

of study design and conduct, to provide a gle summary indicator of study quality However,empirical evidence and theoretical considerations

sin-Systematic reviews and meta-analysis 105

suggest that summary quality scores should not be

used to assess the quality of trials in systematic

re-views Rather, the relevant methodological aspects

should be identified in the study protocol, and

as-sessed individually

At a minimum, a narrative summary of the

re-sults of the quality assessment should be

pre-sented, ideally supported by a tabular or graphical

display Ideally, the results of the quality

assess-ment should be incorporated into the review for

example by stratifying analyses according to

sum-mary risk of bias or restricting inclusion in the

re-view or primary analysis to studies judged to be at

low risk of bias for all or specified criteria

Associa-tions of individual items or summary assessments

of risk of bias with intervention effect estimates

can be examined usingmeta-regression analyses

(a statistical method to estimate associations of

study characteristics (‘moderator variables’) with

intervention effect estimates), but these are often

limited by low power Studies with a rating of high

or unclear risk of bias/concerns regarding

applica-bility may be omitted, insensitivity analyses

Example: The Lawlor and Hopker (2001) review

assessed trial quality by noting whether

alloca-tion was concealed, whether there was blinding,

and whether an intention to treat analysis was

re-ported They conducted meta-regression analyses

(see ‘Heterogeneity between study results’ section,

pp 106–108, below) to investigate the influence of

these quality items on summary estimates of

treat-ment effect

How do we synthesise

findings across studies?

Where possible, results from individual studies

should be presented in astandardised format,

to allow comparison between them If the

end-point is binary (for example, disease versus no

dis-ease, or dead versus alive) then risk ratios, odds

ratios or risk differences may be calculated

Empir-ical evidence shows that, in systematic reviews of

randomised controlled trials, results presented as

risk ratios or odds ratios are more consistent than

those expressed as risk differences

If the outcome is continuous and measurements

are made on the same scale (for example, blood

pressure measured in mm Hg) then the

interven-tion effect is quantified as the mean difference

between the intervention and control groups Ifdifferent studies measured outcomes in differentways (for example, using different scales for mea-suring depression in primary care) it is necessary

to standardise the measurements on a commonscale to allow their inclusion in meta-analysis This

is usually done by calculating the standardised mean differencefor each study (the mean differ-ence divided by the pooled standard deviation ofthe measurements)

Example: In the Lawlor and Hopker (2001) review,

the primary outcome of interest, depression score,was a continuous measure assessed using differentscales Standardised mean differences were there-fore calculated for each study

Meta-analysis

Ameta-analysisis a statistical analysis that aims

to produce a single summary estimate by ing the estimates reported in the included stud-ies This is done by calculating a weighted av-erage of the effect estimates from the individualstudies (for example, estimates of the effect of theintervention from randomised clinical trials, or es-timates of the magnitude of association from epi-demiological studies) Ratio measures should belog-transformed before they are meta-analysed:they are then back-transformed for presentation ofestimates and confidence intervals For example,

combin-denoting the odds ratio in study i by OR iand the

weight in study i by w i, the weighted average logodds ratio is

corre-The choice of weight depends on the choice ofmeta-analysis model Thefixed effectmodel as-sumes the true effect to be the same in each study,

so that the differences between effect estimates

in the different studies are exclusively due to

ran-dom (sampling) variation.Random-effects

meta-analysis models allow for variability between the

true effects in the different studies Such

variabil-ity is known asheterogeneity, and is discussed in

more detail below

In fixed-effect meta-analyses, the weights are

based on theinverse varianceof the effect in each

study:

w i= 1

v i

where the variance vi is the square of the

stan-dard error of the effect estimate in study i

Be-cause large studies estimate the effect precisely

(so that the standard error and variance of the

ef-fect estimate are small), this approach gives more

weight to the studies that provide most

informa-tion Other methods for fixed-effect meta-analysis,

such as the Mantel-Haenszel method or the Peto

method are based on different formulae but give

similar results in most circumstances

In a random-effects meta-analysis, the weights

are modified to account for the variability in

true effects between the studies This

modifica-tion makes the weights (a) smaller and (b)

rela-tively more similar to each other Thus,

random-effects meta-analyses give relatively more weight

to smaller studies The most commonly used

method for random-effects meta-analysis was

proposed by DerSimonian and Laird The

sum-mary effect estimate from a random-effects

meta-analysis corresponds to the mean effect, about

which the effects in different studies are assumed

to vary It should thus be interpreted differently

from the results from a fixed-effect meta-analysis

Example: The Lawlor and Hopker review used

a fixed effect inverse variance weighted

meta-analysis when heterogeneity could be ruled out,

otherwise a DerSimonian and Laird random effects

model was used

Forest plots

The results of a systematic review and

meta-analysis should be displayed in aforest plot Such

plots display a square centred on the effect

esti-mate from each individual study and a horizontal

line showing the corresponding 95% confidence

intervals The area of the square is proportional to

its weight in the meta-analysis, so that studies that

contribute more weight are represented by larger

squares A solid vertical line is usually drawn torepresent no effect (risk/odds ratio of 1 or meandifference of 0) The result of the meta-analysis

is displayed by a diamond at the bottom of thegraph: the centre of the diamond corresponds tothe summary effect estimate, while its width cor-responds to the corresponding 95% confidence in-terval A dashed vertical line corresponding to thesummary effect estimate is included to allow vi-sual assessment of the variability of the individualstudy effect estimates around the summary esti-mate Even if a meta-analysis is not conducted, it

is often still helpful to include a forest plot out a summary estimate, in which case the sym-bols used to display the individual study effect es-timates will all be the same size

with-Example: Figure 12.2 shows a forest plot, based on

results from the Lawler and Hopker (2001) review,

of the effect of exercise compared to no treatment

on change in depressive symptoms, measured ing standardised mean differences The summaryintervention effect estimate suggests that exercise

us-is associated with an improvement in symptoms,compared to no treatment

Heterogeneity between study results

Before pooling studies in a meta-analysis it is portant to consider whether it is appropriate to

im-do so If studies differ substantially from one other in terms of population, intervention, com-parator group, methodological quality or study de-sign then it may not be appropriate to combinetheir results It is also possible that even whenthe studies appear sufficiently similar to justify ameta-analysis, estimates of intervention effect dif-fer to such an extent that a summary estimate isnot appropriate or should accommodate these dif-ferences Differences between intervention effectestimates greater than those expected because ofsampling variation (chance) are known as ‘statis-tical heterogeneity’ As part of the process of con-ducting a meta-analysis, the presence of hetero-geneity should be formally assessed The first step

an-is van-isual inspection of the results dan-isplayed in theforest plot On average, in the absence of hetero-geneity, 95% of the confidence intervals aroundthe individual study estimates will include thefixed-effect summary effect estimate The secondstep is to report a measure of heterogeneity, and ap-value from a test for heterogeneity

Systematic reviews and meta-analysis 107

Study (No of weeks of intervention)

Diamond shows summary intervention effect estimate across studies Centre of diamond is the intervention effect estimate, tips of diamond indicate upper and lower confidence limits

Standardised mean difference in effect size

2

for depression

Heterogeneity can be quantified using the τ2

or I2 statistics The τ2 statistic represents the

between-study variance in the true intervention

effect, and is used to derive the weights in a

random-effects meta-analysis A disadvantage is

that it is hard to interpret, although it can be

con-verted to provide a range within which we expect

the true treatment effect to fall (for example a 90%

range for the mean difference) The I 2 statistic

quantifies the percentage of total variation across

studies that is due to heterogeneity rather than

chance I2 lies between 0% and 100%; a value

of 0% indicates no observed heterogeneity, and

larger values show increasing heterogeneity When

I2= 0 then τ2= 0, and vice-versa

A statisticaltest for heterogeneityis a test of the

null hypothesis that there is no heterogeneity, i.e

that the true intervention effect is the same in all

studies (the assumption underlying a fixed-effect

meta-analysis) A test for heterogeneity proceeds

by deriving aQ-statistic, whose value is not in

it-self of interest but which can be compared with

theχ2 distribution in order to derive a p-value

As usual, the smaller the p-value the stronger is

the evidence against the null hypothesis Hence,

a small p-value from a test for heterogeneity

sug-gests that the true intervention effect varies

be-tween the studies Tests for heterogeneity should

be interpreted with caution, because they typically

have low power

If heterogeneity is present then a small

number of (ideally pre-specified) subgroup

and/or sensitivity analyses can be conducted to

investigate whether the treatment effect differsacross subgroups of studies (for example, thoseusing high versus low dose of the intervention orthose assessed as at high compared to low risk

of bias) However, typical meta-analyses containfewer than 10 component studies, which severelylimits the potential for these additional analyses toprovide definitive explanations for heterogeneity

If heterogeneity remains unexplained but pooling

is still considered appropriate, arandom effects analysis can be used to accommodate hetero-geneity, though its results should be interpreted

in the light of the underlying assumption thatthe true intervention effect varies between thestudies Alternatively, it may be appropriate topresent a narrative synthesis of findings acrossstudies, without combining the results into asingle summary estimate

Example: There was substantial variability

be-tween the results of the studies of exercise pared with no treatment for depression that werelocated by Lawlor and Hopker (2001) (Figure 12.2).Four of the 10 confidence intervals around thestudy effect estimates did not include the sum-mary effect estimate This visual impression wasconfirmed by strong evidence of heterogeneity(Q= 35.0, P < 0.001) The estimated value of the

com-between-study variance was τ2 = 0.41 Lawlorand Hopker reported results from a random-effects meta-analysis, and used meta-regressionanalyses to investigate heterogeneity due toquality features (allocation concealment, use ofintent-to-treat analysis, blinding), setting, baseline

depression severity, type of exercise, and type of

publication As shown in Figure 12.2, intervention

effect estimates were greater in two studies that

were published only as conference abstracts than

in the studies published as full papers

Reporting biases

The dissemination of research findings is a

con-tinuum ranging from the sharing of draft papers

among colleagues, presentations at meetings,

publication of abstracts, to availability of full

papers in journals that are indexed in the major

bibliographic databases Not all studies are

pub-lished in full in an indexed journal and therefore

easily identifiable for systematic review Reports

of large externally funded studies with

statis-tically significant results are more likely to be

published, published quickly, published in an

English-language journal, published in more than

one place, and cited in subsequent publications

and so their results are more accessible and easy

to locate Reporting biases are introduced when

the publication of research findings is

influ-enced by the strength and direction of results

Publication biasrefers to the nonpublication of

whole studies, whilelanguage biascan occur if a

review is restricted to studies reported in specific

languages For example, investigators working

in a non-English-speaking country may be more

likely to publish positive findings in international,

English-language journals, while sending less

interesting negative or null findings to

local-language journals It follows that restricting a

review to English-language publications has the

potential to introduce bias Even when a study

is published, selective reporting of outcomes has

the potential to lead to serious bias in systematic

reviews

Reporting biases may lead to an association

be-tween study size and effect estimates Such an

as-sociation will lead to an asymmetrical appearance

of a funnel plot – a scatter plot of a measure of

study size against effect estimate (the lighter

cir-cles in the upper panel of Figure 12.3 are the results

of unpublished studies that will be missing in the

funnel plot) Thereforefunnel plots(Figure 12.3),

and statistical tests for funnel plot asymmetry, can

be used to investigate evidence of reporting

bi-ases However, it is important to realise that

fun-nel plot asymmetry can have causes other than

re-porting biases: for example that poor

methodolog-ical quality leads to spuriously inflated effects in

Symmetricalfunnel plot

No small study effect

evidence of small study effect

smaller studies, or that effect size differs according

to study size because of differences in the intensity

of interventions

Presenting the results of the review

A systematic review should present overviews

of the characteristics, quality and results of theincluded studies Tabular summaries are veryhelpful for providing a clear overview Types ofdata that may be summarised include details ofthe study population (setting, demographic fea-tures, presenting condition details), intervention(e.g dose, method of administration), comparatorinterventions, study design, outcomes evaluatedand results Depending on the amount of data to

be summarised it can be helpful to include rate tables for baseline information, study quality,

sepa-Systematic reviews and meta-analysis 109

and study results The narrative discussion should

consider the strength of the evidence for a

treat-ment effect, whether there is unexplained

varia-tion in the treatment effect across individual

stud-ies, and should incorporate a discussion of the risk

of bias and applicability of the included studies If

meta-analysis is not possible, for example because

outcomes assessed in the included studies were

too different to pool, then the narrative discussion

is the main synthesis of results across studies It

is important to provide some synthesis of results

across studies, even if this is not statistical, rather

than simply describing the results of each included

study

Example: Table 12.1 shows an extract from the

study details table reported in the Lawlor and

Hop-ker (2001) review This table allows the reader to

quickly scan both the characteristics of individual

studies (rows) and the pattern of a characteristic

across the whole review (columns)

Critical appraisal of

systematic reviews

When reading a report of a systematic review the

following criteria should be considered:

(1) Is the search strategy comprehensive, or could

some studies have been missed?

(2) Were at least two reviewers involved in all

stages of the review process (reference

screen-ing, inclusion assessment, data extraction and

quality assessment)?

(3) Was study quality assessed using appropriate

criteria?

(4) Were the methods of analysis appropriate?

(5) Is there heterogeneity in the treatment effect

across individual studies? Is this investigated?

(6) Could results have been affected by reporting

biases or small study effects?

If a systematic review does not report sufficient

detail to make a judgment on one or more of

these items then conclusions drawn from the

re-view should be cautious The PRISMA statement is

a 27-item checklist that provides guidance to

sys-tematic review authors on what they should

re-port in journal articles It is not a critical appraisal

checklist, but reports following PRISMA should

give enough information to permit a

comprehen-sive critical appraisal of the review

KEY LEARNING POINTS

r Systematic reviews are ‘studies of studies’ that

follow a defined structure to identify, evaluate and summarise all available evidence addressing a particular research question

r Key characteristics of a systematic review

include a set of objectives with pre-defined inclusion criteria, explicit and reproducible methodology, comprehensive searches that aim

to identify all relevant studies, assessment of the quality of included studies, and a standardised presentation and synthesis of the characteristics and findings of the included studies

r Meta-analysis is a statistical analysis that aims

to produce a single summary estimate, with associated confidence interval, based on a weighted average of the effect size estimates from individual studies

r Heterogeneity is variability between the true

effects in the different studies

Acknowledgements

We thank Chris Metcalfe and Matthias Egger forsharing lecture materials that contributed to thischapter

Centre for Reviews and Dissemination (2009)

Sys-tematic Reviews: CRD’s Guidance for ing Reviews in Health Care York: CRD, Univer-

Undertak-sity of York

Systematic reviews and meta-analysis 111

Higgins JPT, Altman DG, Gotzsche PC, Juni P,

Moher D, Oxman AD, et al (2011) The Cochrane

Collaboration’s tool for assessing risk of bias in

randomised trials BMJ 343: d5928.

Higgins JPT, Green S (2011) Cochrane Handbook

for Systematic Reviews of Interventions Version

5.1.0 The Cochrane Collaboration.

Higgins JPT, Thompson SG, Deeks JJ, Altman

DG (2003) Measuring inconsistency in

Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones

DR, Lau J, et al (2011) Recommendations for

ex-amining and interpreting funnel plot try in meta-analyses of randomised controlled

asymme-trials BMJ 343: d4002.

In this chapter you will learn:

✓ to explain basic concepts of economics and how they relate to health;

✓ to distinguish the main types of economic evaluation;

✓ to understand the key steps in costing health care;

✓ to understand the Quality Adjusted Life Year (QALY) and its limitations;

✓ to interpret the results of an economic evaluation.

What is economic

evaluation?

Economic evaluation is the comparison of the

costs and outcomes of two or more alternative

courses of action If you bought this book, you have

already conducted an informal economic

evalua-tion This involved comparing the cost of this book

and the expected benefits of the information it

contains against the cost and expected benefits of

alternative books on the topic In health, economic

evaluation commonly compares the cost and

out-comes of different methods of prevention,

is free or heavily subsidised at the time of use

We never know its cost, and we do not considerwhether it is public money well spent

Epidemiology, Evidence-based Medicine and Public Health Lecture Notes, Sixth Edition Yoav Ben-Shlomo, Sara T Brookes and Matthew Hickman.



Uni ted K

Austr alia (2009)

lic Finlan

d Chile

Lux embou

countries in 2010 (When 2010 data were unavailable, previous years data were used as indicated in parentheses.)

Source: Based on data from OECD (2012) Total expenditure on health, Health: Key Tables from OECD, No 1.

http://dx.doi.org/10.1787/hlthxp-total-table-2012-1-en and OECD (2012) Public expenditure on health, Health: Key Tables

from OECD, No 3 http://dx.doi.org/10.1787/hlthxp-pub-table-2012-1-en

Health care use is often initiated by a

pa-tient deciding to see a doctor In a system with

‘free’ care, this decision can be based on

med-ical and not financial considerations This

cre-ates more equitable access; however it may lead

to overuse of health services for trivial reasons,

sometimes referred to as moral hazard During

the medical consultation, treatment decisions are

often taken by the doctor with some patient

in-put Decisions should be based on sound

evi-dence about treatment effectiveness for the

pa-tient (evidence-based medicine) and affordability

for the population In practice they may also be

ad-versely influenced by incomplete evidence,

com-mercial marketing, and even financial incentives

if doctors are paid per procedure (sometimes

re-ferred to assupplier induced demand) By

pro-viding high-quality evidence on the costs and

out-comes of alternative ways of providing health care,

economic evaluation aims to improve the health

of the population for any fixed level of public

expenditure

The design of an economic evaluation

Key elements of study design discussed in vious chapters also apply to economic stud-

pre-ies For example, a specification of the Patient group, Intervention, Comparator(s) and Outcome (PICO – see Chapter 8) is essential In economic

evaluation the outcome of interest is frequently pressed as a ratio, such as the additional cost perlife year gained

ex-An economic evaluation conducted side a randomised controlled trial (RCT) would,typically, provide stronger evidence than an eval-uation based on a cohort study Regrettably, manyRCTs do not include an economic evaluation,although regulators are increasingly demand-ing proof of efficiency before approval of newdrugs and devices In the absence of relevantinformation from RCTs, policy-makers rely on

along-Analgesic A

>=50% pain relief

Cost_drug A + Other_Costs_Success

Cost_drug B + Other_Costs_SuccessCost_drug A + Other_Costs_Fail

Cost_drug B + Other_Costs_Fail

Prob_A

Prob_B 1-Prob_A

1-Prob_B

>=50% pain relief

<50% pain relief

<50% pain reliefAnalgesic B

Patients with pain

The probability of successful pain relief with drug A (Prob_A) and drug B (Prob_B) can be estimated from RCTs or the bestavailable observational data If economic data from an RCT are unavailable, the costs of prescribing drugs A and B(Cost_drugA and Cost_drugB) and the other costs of treating patients with successful (Other_Costs_Success) andunsuccessful (Other_Costs_Fail) pain relief can be estimated from observational studies These six parameters allowestimation of the additional cost per patient with substantial pain relief of drug A versus drug B

For example if: Prob_A= 0.75; Prob_B = 0.50; Cost_drugA = £100; Cost_drugB = £50; Other_Costs_Success = £20and Other_Costs_Fail= £40, then the cost effectiveness of drug A versus drug B is:

[(£100+ (0.75)∗£20+ (1 − 0.75)∗£40)− (£50 + (0.50)∗£20+ (1 − 0.50)∗£40)]/(0.75 − 0.50)

This equates to£180 for every additional patient with substantial pain relief from drug A

economic evidence generated by decision analysis

models These models define the possible clinical

pathways resulting from alternative interventions

(Figure 13.2) and then use literature reviews to

draw together the best available evidence on

the probability of each pathway, the expected

costs and impact on patient health Clearly these

models are only as valid as the studies upon which

they are based

Efficiency is in the eye of

the beholder

It is essential to consider the boundaries of the

economic evaluation A programme to prevent

obesity in children is unlikely to appear

cost-effective during the first few years, but may prove

a wise investment over subsequent decades as

the cohort develops fewer weight-related diseases

Therefore, for chronic diseases the appropriate

time horizon for the economic evaluation is

of-ten the lifetime of the patient group This has

important implications for expensive new

treat-ments where effectiveness can be proven relatively

quickly by an RCT, but efficiency may not

be-come apparent until long after the end of the RCT

follow-up

A natural starting point for an integrated health

system is to ask whether the money it spends on

a health technology is justified by the ment it achieves in patient health However, thishealth-system perspective may inadvertently lead

improve-to blinkered decision making, whereby costs areshifted onto other elements of society For examplecentralisation of health care into larger clinics orhospitals might save the health system money atthe expense of patients, carers and society throughgreater travel costs and more time off work Giventhis, a strong argument can be made that, in mak-ing public spending decisions, we should take anall-encompassing (societal) viewpoint

In everyday life, we are accustomed to ing about costs in terms of monetary values.However money is just an imperfect indicator

think-of the value think-of the resources used For ple, a doctor-led clinic-based routine follow-up

exam-of women with breast cancer could be replacedwith a nurse-led telephone based approach Thefinancial cost of the doctor-led clinics may be nohigher than the nurse-led telephone follow-up ifthe clinics are of short duration and conducted

by low-salaried junior doctors However, the true

opportunity cost of the doctor led clinics may

be much higher if these routine follow-up visitsare preventing other women with incident breastcancer receiving prompt treatment at the clinic.The concept of opportunity cost acknowledgesthat the true cost of using a scarce resource inone way is its unavailability to provide alternativeservices

Health economics 115

How much does it cost?

The costing process involves identification of

resource items affected by the intervention,

mea-surement of patient use of these items and

val-uation to assign costs to resources used

Identi-fication is governed by the chosen perspective of

the analysis From a health system perspective,

an evaluation of a new drug for multiple

sclero-sis would go no further than tracking patient use

of community, primary and secondary care health

services A broader societal perspective would

re-quire additional information on lost productivity

due to ill health, care provided by friends and

fam-ily and social services, and patient expenses

re-lated to the illness (e.g travel to hospital, purchase

of mobility equipment)

The introduction of electronic records has

greatly increased the potential to use routinely

col-lected data to measure resources (e.g tests,

pre-scriptions, procedures) used in hospitals and

pri-mary care However, there are drawbacks Records

are often fragmented across different health

sys-tem sectors and difficult to access Records are

usually established for clinical and/or payment

purposes rather than research and therefore may

not contain sufficient information for accurate

costing Therefore, patient self-report in the form

of questionnaires or diaries is often used, but may

be affected byloss to follow-up and recall bias

The degree of detail required for costing will vary A

study evaluating electronic prescribing would

re-quire direct observation of the prescription

pro-cess In other studies such minute detail on the

du-ration of a clinic visit would be unnecessary

Many health systems publish the unit costs of

health care, for example the average cost of a MRI

scan of the spine, which can be used to valuethe resources used by patients However, in anRCT comparing rapid versus conventional MRI ofthe spine an average cost would not be sufficientand a unit cost must be calculated from scratch.This would include allocating the purchase cost

of the imaging equipment across its lifetime nuitisation) and apportioning salaries, mainte-nance, estate and other costs to every minute ofmachine use It is particularly difficult to gener-alise the valuation of resource use between na-tions General practitioners in the United States,United Kingdom and the Netherlands are paid up

(an-to twice as much as their counterparts in Belgiumand Sweden, even after adjusting for the cost ofliving

Is it worth it?

The typical goal of an intervention is to use sources to optimise health measured by clinicaloutcomes such as mortality or bone density, orpatient-reported outcomes such as pain or qual-ity of life (known astechnical efficiency) If oneoutcome is of overriding importance then aCost Effectiveness Analysis (CEA)(Table 13.1) could beused to summarise whether any additional costs

re-of the intervention are justified by gains in health.For example an evaluation of acupuncture versusconventional care for patients with pain could cal-culate the extra cost per additional patient whohas a 50% reduction in pain score at 3 months Ifmore than one aspect of health, for instance pain

and function, are considered important outcomes

of treatment, analysts can choose to simply late the costs and all outcomes in aCost Conse- quences Study (CCS) In a CCS, the reader is left

tabu-Table 13.1 Types of economic evaluation.

Cost-effectiveness analysis A primary physical measure e.g 50%

reduction in pain score

Extra cost per extra unit of unit ofprimary outcome measureCost consequences study More than one important outcome

measure e.g 50% reduction in painscore, 50% increase in mobility scoreand patient satisfaction score

Costs and outcomes are presented

in tabular form with no aggregation

a if no intervention is dominant.

to weigh up the potentially conflicting evidence on

disparate cost and outcomes to reach a conclusion

about the most efficient method of care

Less frequently, analysts useCost Benefit

Anal-ysis (CBA)to place a monetary value on treatment

programmes This is simplest in areas where

citi-zens are familiar with paying for care For example,

people who might benefit from a new type of In

Vitro Fertilisation (IVF) could be asked how much

they would be willing to pay (WTP) for a cycle of

this therapy, based on evidence that it increases

the chances of birth from 20% to 30% If the WTP

of those who might benefit is greater than the

ad-ditional costs of this new type of IVF, then this

pro-vides evidence that it is an efficient use of health

care resources

Policy-makers aim to create a health care

sys-tem that is bothtechnically and allocatively

effi-cient This means that money spent on each

sec-tor of care (e.g oncology, orthopaedics or mental

health) would not result in more health benefits if

reallocated elsewhere in the health system These

allocative comparisons would be aided by a

uni-versal outcome measure This measure needs to be

flexible enough to be applicable in trials with

out-comes as diverse as mortality, depression, and

vi-sion.Quality Adjusted Life Years (QALYs)used in

Cost-Utility Analysis (CUA)aim to provide such a

universal measure (see Table 13.1 which compares

the 4 different types of analysis)

What is a QALY?

QALYs measure health outcomes by weighting

years of life by a factor (Q) that represents the

pa-tient’s health-related quality of life Q is anchored

at 1 (perfect health) and 0 (a health state

consid-ered to be as bad as death) and is estimated for all

health states between these extremes and a small

number of health states that might be considered

worse than death A QALY is simply the number

of years that a patient spends in each health state

multiplied by the quality of life weight, Q, of that

state For example, a patient who spends 2 years in

an imperfect health state, where Q= 0.75, would

achieve 1.5 QALYs (0.75× 2) Q is generally

esti-mated indirectly via a questionnaire such as the

EQ-5D The questionnaire asks the patient to

cat-egorise current health in various dimensions – for

example, mobility, pain, and mental health Every

possible combination of questionnaire response is

given a quality weight, Q These weights are rived from surveys of the public’s valuations for thehealth states described by the questionnaire.There are concerns that in the attempt to mea-sure and value a very broad range of dimensions

de-of health, QALY questionnaires such as the 5D have sacrificed responsiveness to small butimportant changes within an individual dimen-sion Additionally, there is disagreement about theappropriate group to use in the valuation sur-vey Should it be the general population who cantake a dispassionate, but perhaps ill-informed, ap-proach to valuing ill health? Or should it be pa-tient groups who have experienced the healthstate? Perhaps the most persistent question aboutQALYs is whether they result in fair interpersonalcomparisons of treatment effectiveness The CUAmethodology typically does not differentiate be-tween a QALY resulting from treatment of a con-genital condition in a child and a QALY resultingfrom palliative care in an elderly patient with a ter-minal illness It is debatable whether this neutralstance reflects public opinion For these and otherreasons, QALYs remain controversial; in the UKthey currently play an important role in nationalhealth care decision making, whereas in Germanytheir role is less prominent

EQ-What are the results of an economic evaluation?

In essence, there are only four possible resultsfrom an economic evaluation of a new interven-tion versus current care (Cost Effectiveness Plane (CEP); (Figure 13.3)) Many new drugs are in theNorth East (NE) quadrant; they are more expen-sive, but more effective than existing treatmentoptions But that need not be the case ‘Break-through’ drugs (e.g Penicillin) can be both effec-tive and cost saving (i.e dominant in the SouthEast quadrant) if the initial cost of the drug is re-couped through future health care avoided Whenthe most effective intervention is simply not af-fordable, policy makers may opt for an interven-tion in the South West quadrant which is slightlyless effective but will not bankrupt the health sys-tem Sadly, the history of medicine also has a num-ber of examples of new technologies (e.g Thalido-mide for morning sickness) that fall into the NorthWest quadrant, more costly and eventually seen to

be harmful (i.e dominated) Most controversy and

headlines in high-income countries concern

inter-ventions in the NE quadrant Can public funds

af-ford to pay for all health care that is effective, no

matter how expensive or marginally effective it is?

Assuming that the answer is no, then one

solu-tion for differentiating between more efficient and

less efficient innovations would be to define a

cost-effectiveness threshold For example, the UK

Gov-ernment has indicated that it is unwilling to fund

interventions that yield less than one QALY per

£30,000 spent (i.e anything above and to the left

of the dashed line in Figure 13.3)

The key finding of an economic evaluation is

of-ten summarised in anIncremental Cost

Effective-ness Ratio (ICER) This is simply the difference in

cost between the intervention and the comparator(Ci– Cc) divided by the difference in effectiveness(Ei– Ec) A worked example, based on a UK eval-uation of a new drug for advanced liver cancer, isprovided in Table 13.2 In that example, the drugwas effective, but the large additional cost resulted

in a high ICER suggesting that it might not be anefficient use of public money

In countries such as the UK where there is arelatively established threshold, the ICER is com-monly converted into a Net Monetary Benefit (NMB)statistic (Table 13.2) The NMB is attractivebecause it simplifies interpretation, a new treat-ment with a negative NMB is not cost-effective,and enables straightforward calculation of confi-dence intervals

Table 13.2 Worked example of calculating the ICER and NMB.

NMB(30,000) (1.08− 0.72)∗£30,000− (£28,359 − £9,739) = −£7,820

ICER =Incremental cost-effectiveness ratio

NMB(30,000)= net monetary benefit statistic (at a £30,000 threshold)

Cost per QALY threshold

Cost-effectiveness acceptability curve – drug A

Cost per QALY threshold

Cost-effectiveness acceptability curve – drug B

0.00

Note: The probability that a drug is cost-effective can be estimated by plotting a line up from a chosen threshold on thehorizontal axis (e.g.£30,000 per QALY) to the curve and then across to read off the probability from the vertical axis Anapproximate lower (and upper) 95% confidence limit can be estimated by plotting a line across from 0.025 (0.975) on thevertical axis to the curve and then down to read off the cost per QALY limit from the horizontal axis

Health economics 119

Interpreting the result

Thecost effectiveness acceptability curve (CEAC)

(Figure 13.4) is becoming a popular way of

pre-senting the degree of certainty about the result

of an economic evaluation These graphs can

be interpreted by scanning across the horizontal

axis to a conventional cost-effectiveness threshold

(£30,000 per QALY in the UK) and reading off the

associated probability of cost-effectiveness from

the vertical axis In Figure 13.4, both drugs A and

B are probably not cost-effective at the

recom-mended threshold (p<0.50) However while drug A

is almost certainly not cost-effective (approximate

95% confidence interval of £31,000 to £72,000 per

QALY), the case is far from proven for drug B

(approximate 95% confidence interval of £12,000

to £91,000 per QALY) A larger RCT with longer

follow-up might provide a more definitive answer

Uncertainty can also be addressed through

sen-sitivity analysis where key assumptions of the

analysis, for example the drug or device cost, are

varied to determine the robustness of conclusions

What happens next?

Even if the benefits of an intervention have been

clearly shown to justify the costs these results form

just one part of the decision-making process

Polit-ical objectives such as promotion of equality and

budgetary considerations (i.e what will we stop

doing in order to afford this new treatment?) will

also be taken into account before the intervention

is recommended

Summary

Economic evaluation is a key component of

evidence-based medicine It represents a shift in

thinking away from ‘what is the most effective way

of improving this patient’s health?’ and towards

‘what is the most efficient way of using a

health-care budget to optimise the health and wellbeing

of the population?’

KEY LEARNING POINTS

r Economic evaluations allow one to make

rationale choices between treatments

r Costs and benefits are commonly calculated

from a health system or societal perspective

r Costing requires identification, measurement

and valuation of resources

r There are four main types of economic

evaluation: cost-effectiveness, cost-consequence, cost-benefit and cost-utility analysis

r QALYs combine health-related quality of life and

survival, enabling comparison of treatments across different domains of health care with a common metric

r An economic evaluation may indicate that a new

intervention is dominant (effective and cost-saving), dominated (ineffective and costly)

or effective but more expensive

r The trade off between the costs and

effectiveness of therapies can be summarised

by the Incremental Cost Effectiveness Ratio and Net Monetary Benefit statistic

r Statistical uncertainty can be quantified using a

confidence interval or Cost Effectiveness Acceptability Curve

r Sensitivity analyses are usually undertaken to

see if the conclusions are robust to various assumptions

FURTHER READING

Drummond MF, Sculpher MJ, Torrance GW,

O’Brien BJ, Stoddart GL (2005) Methods for

the Economic Evaluation of Health Care grammes Oxford: Oxford University Press.

Pro-Drummond MF, Richardson WS, O’Brien BJ,Levine M, Heyland D (1997) Users’ guides tothe medical literature XIII How to use an ar-ticle on economic analysis of clinical practice

A Are the results of the study valid?

Evidence-Based Medicine Working Group JAMA 277:

1552–7

O’Brien BJ, Heyland D, Richardson WS, Levine M,Drummond MF (1997) Users’ guides to the med-ical literature XIII How to use an article on eco-nomic analysis of clinical practice B What arethe results and will they help me in caring for

my patients? Evidence-Based Medicine Working

Group JAMA 277: 1802–6.

Ramsey S, Willke R, Briggs A, et al (2005) Good

research practices for cost-effectiveness sis alongside clinical trials: the ISPOR RCT-CEA

analy-Task Force report Value Health 8: 521–33.

In this chapter you will learn:

✓ how to describe the process around the audit cycle;

✓ what the general ethical principles are around research;

✓ what is the role of the research ethics committee;

✓ what special issues relate to interventional and observational studies;

✓ the principles around research with children and incapacitated

adults.

How do we know we are

doing a good job?

It is common for health care professionals to

re-view the management of patients when something

goes very wrong, such as an unexpected death or

serious complication post-surgery (critical

inci-dent analysis) However problems with more

mi-nor events, e.g wound infection rates, or mortality

in high-risk patients may not be detected without

some sort of formal audit procedure which is

in-tended to detect ‘outliers’ These can be both

posi-tive (better than expected) or negaposi-tive (worse than

expected) rates of events and the unit of analysis

could be at the level of an individual clinician, cialty within a hospital level or at a hospital level.For example the Bristol Royal Infirmary enquiryinvestigated an excess number of children underthe age of one dying from open heart surgery be-tween 1991 and 1995 (between 30 and 35 addi-tional deaths) It concluded

spe-There was no systematic mechanism for monitoring the clinical performance of healthcare profession- als or of hospitals For the future there must be ef- fective systems within hospitals to ensure that clin- ical performance is monitored There must also be

a system of independent external surveillance to view patterns of performance over time and to iden- tify good and failing performance (www.bristol- inquiry.org.uk/)

re-Epidemiology, Evidence-based Medicine and Public Health Lecture Notes, Sixth Edition Yoav Ben-Shlomo, Sara T Brookes and Matthew Hickman.



Audit, research ethics and research governance 121

The audit cycle

Auditis a form of quality improvement that aims

to improve clinical care by critically examining

ex-isting practice and identifying any areas for

con-cern The necessary steps involve:

(1) choosing a topic for the audit;

(2) predefining acceptable standards or using the

variation in the distribution of outcomes to

identify outliers (see Figure 14.1);

(3) collecting relevant data to address the topic

including information on case mix or clinical

severity;

(4) analysing the data so that performance is

compared to expected outcomes;

(5) implementing any necessary

recommenda-tions;

(6) repeating audit after a sufficient time period to

enable any improvement to occur

What’s the difference

between audit, service

evaluation and research?

Unlike research, audit by definition is not designed

to obtain new evidence but rather compares

actual performance with some agreed level ofquality standards The findings may be unique tothe individual hospital or health care system andnot generalisable to other situations Its aim is toimprove health care delivery rather than identifynew risk factors or new interventions that work

It is concerned with the appropriate tation of evidence or consensus based guidelinesrather than their development It usually uses ex-isting data rather than collecting new data thoughthe process of extracting that data may be similar

implemen-to that used in research.Service evaluationcan beconsidered even one stage earlier than audit as itsprimary purpose is simply to measure what andhow services are actually delivered without refer-ence to any specific quality standard as in audit.Both audit and research, however, may have eth-ical implications (see below) though usually au-dit and service evaluation do not require formalethical review by a research ethics committee Ap-pendix 14.1 highlights the differences between re-search, audit and service evaluation

Ethical issues

Research ethics can be defined as the sustainedanalysis of motives of, procedures for and so-cial effects of biomedical research (Murphy, 2004,

renal replacement therapy across different renal units in the United Kingdom The x-axis indicates whether the unit is large orsmall and the graph shows different confidence intervals so one can infer the probability that the result may have occurred

by chance There are four high performing units and one low performing unit outside the 99.9% confidence limits

Source: taken from Hodsman A, Ben-Shlomo Y, Roderick P et al (2011) The ‘centre effect’ in nephrology: what do

differences between nephrology centres tell us about clinical performance in patient management? Nephron Clin Pract 119:

c10–c17 Reproduced with permission from S Karger AG Basel

Image not available in this digital edition.

p 1) Any clinical, biomedical, epidemiological or

social-science research which involves direct

con-tact with NHS patients or healthy participants

should be undertaken in accordance with

com-monly agreed standards of good ethical practice

The Declaration of Helsinki, first written in 1963 by

the World Medical Association, lays down a set of

ethical principles for medical research The

funda-mental and widely accepted ethical principles can

be broadly classified as:

r Beneficence (to do good)

r Nonmaleficence (first, do no harm)

r Autonomy (individual’s right to choose)

r Justice (fairness and equality)

r Truthfulness (informed consent,

confidential-ity)

Historical events, such as the Nuremberg Trials

(Nazi doctors experimented on prisoners under

the pretext of medical research) and the Tuskegee

syphilis study (where African-American men with

syphilis were never asked for consent and had

penicillin knowingly withheld after its

introduc-tion so that doctors could study the natural history

of the disease), led to the need for a statement

of ethical issues in research, such as the

Decla-ration of Helsinki, and for arrangements for the

ethical review of proposed research in order to

protect the research participants and promote

high-quality research

For research involving patients of the United

Kingdom National Health Service (NHS), their

tis-sue or their data, ethical review and favourable

ethical opinion is sought prospectively from an

NHS Research Ethics Committee Research

under-taken by academic staff or students involving

par-ticipants outside of the NHS should be reviewed

by ethical committees within the host Higher

Ed-ucation Institution Ethical review must occur

be-fore any research related activity takes place Other

developed countries have different but equivalent

bodies such as Institutional Review Boards (IRBs)

in the United States or Independent Ethics

Com-mittees Ethics committees must not only

con-sider key ethical aspects of the research but also

its validity; poor quality research can be

uneth-ical because it may have no benefit in terms of

new knowledge whilst have some risk for the

par-ticipants It may also put future participants at

harm if the research is misleading (for example

the scare concerning MMR vaccination and risk of

autism leading to a decline in population

vaccina-tion rates)

Ethical issues in Randomised Controlled Trials (RCTs)

All research studies raise ethical issues, such as

participant confidentiality However RCTs volve more difficult issues than observationalstudies, because they mean that the choice oftreatment is not made by patients and cliniciansbut is instead devolved to a process of random al-location This means that a patient in an RCT mayreceive a new untested treatment, or not be able tochoose a new active treatment if allocated to theplacebo group

in-Before one can undertake an RCT, the healthprofessionals treating the patients must be un-certain about whether the treatments beingevaluated are better, worse or the same as anyexisting treatment or a placebo This is called

clinical equipoise If there is existing evidencethat a new treatment is superior then cliniciansshould not participate However, in reality, mostclinicians will have some preference or ‘hunch’that one treatment is better than another, butthey will need to suspend these views to conduct

an RCT to provide clear evidence Often, RCTresults are different from clinicians’ hunches.For example a recent large RCT of a drug thatinhibits the cholesteryl ester transfer protein(CETP) and raises HDL-cholesterol, associatedwith a reduced risk of heart disease, actually found

an increased risk of cardiovascular events spite improving HDL-cholesterol, it was unclearwhy patients on active treatment had a highermortality rate though the drug did unexpectedlyraise the participants’ blood pressure (Barter

De-et al., 2007).

As described in more detail below patients mustgiveinformed consentto participate in an RCTand must understand that the treatment they re-ceive will be determined by chance through ran-domisation If one of the treatments is a placebogroup then the patients must know this Theyshould not be coerced to take part or given finan-cial incentive other than any expenses that arisefrom participation Even if they consent to partic-ipate, they are entitled to withdraw from the study

at any time and this should in no way mise their future treatment For informed consent

compro-to be ethically valid the investigacompro-tor must discloseall risks and benefits and the participant must becompetent to understand this Independent re-search ethics committee must review and approvestudies before they are undertaken

Audit, research ethics and research governance 123

One special aspect of RCTs is the use of ‘sham’

procedures to maintain blinding In a drug trial

it is usually straightforward to create an

identi-cal looking placebo so that participants cannot

tell whether they are taking the active or placebo

medication This is more complex for

nonmed-ical interventions, especially surgnonmed-ical

interven-tions In this case a sham procedure may be used

though this may have risk in itself For example,

a RCT of foetal nigral transplantation for

Parkin-son’s disease randomised patients to the insertion

of aborted material using stereotactic surgery The

placebo group underwent the same procedure and

had partial burr holes made in the skull but no

needle or foetal material was inserted (Olanow

et al., 2003).

Ethical issues in observational

studies

Observational studies are usually less problematic

and of lower risk as the researchers simply

mea-sure characteristics of the participants using

ques-tionnaires, tissue, imaging or physiological

mea-sures One issue that may arise in such studies is

opportunistic identification of clinical

abnormal-ities and it is good practice to have an explicit

protocol for how these will be handled as well

as obtaining consent from the participants as to

whether they would wish to have this

informa-tion feedback to them and/or their general

practi-tioners For example many epidemiological

stud-ies will measure blood pressure and there are clear

evidence-based guidelines on what constitutes a

level worthy of treatment if it is sustained over

sev-eral readings or over a 24-hour period However,

studies of MRI brain imaging in the elderly will find

a high prevalence of asymptomatic brain infarcts

(around 18% in subjects between 75 and 97 years

in the Rotterdam study) In this case it is less clear

that feeding back abnormal results is helpful as it

may cause participant anxiety without necessarily

any improvement in health care (Vernooij et al.,

2007)

Informed consent

Informed consent is at the heart of ethical

re-search Most studies involving individuals must

have appropriate arrangements for obtaining

consent from potential research participants formed consent must be:

In-r voluntary and freely given;

writ-Obtaining informed consent should be seen as

a process of communication and discussion tween researcher and participant The researcherhas a duty to ensure the participant truly under-stands what is being asked of them, and that theyare willing to voluntarily give full, informed con-sent Researchers should be very careful not to co-erce the participant or to emphasise the poten-tial benefits, nor attempt to minimise the risks ordisadvantages of participation Coercion may beimplicit rather than explicit if the recruiting clin-ician has a long standing relationship with the pa-tient who may find it hard to refuse the invitation.Participants have the right to ask questions of theresearcher, and be given reasonable time to con-sider their decision to participate before confirm-ing their willingness to participate both verballyand in writing All participants must have given in-formed consent before any aspect of the researchstarts

be-Vulnerable groups (children and

incapacitated adults)

Children

Informed consent must be obtained from thechild’s parent (or legal guardian) as appropriate

When parental consent is obtained, the assent

(voluntary agreement) of the child should also besought by researchers, as appropriate to the child’sage and level of understanding A full explanation

of the research must be given to the parent (or legal

guardian) of the child, in accordance with the

prin-ciples described earlier, including the provision of

written information and opportunity for questions

and time for consideration The parent (or legal

guardian) may then give informed consent for the

child to participate in the study

The child should also be given information

about the research This will be age-appropriate

and offered according to the child’s level of

under-standing Often the use of visual aids or cartoons

can explain basic information for young children

Verbal assent should be sought from the child, and

recorded in the research notes, as well as the child’s

medical record (for clinical trials) Older children

may wish to sign a consent form For children over

the age of 16 this would constitute legally valid

consent

Written information provided to children should

be written in age-appropriate language that the

child could understand Different versions of the

research information should therefore be

pro-duced for different age ranges e.g under 5s, 6–12

year olds, 13–15 year olds and over 16

Incapacitated adults

Incapacitated adults do not have mental

capac-ity to make decisions for themselves This may

be because of unconsciousness, mental illness, orother causes, to the extent that the person does nothave sufficient understanding or ability to make

or communicate responsible decisions Special rangements exist to ensure the interests of inca-pacitated adults recruited into research studiesare protected For investigational medicinal prod-uct (drug) trials, or trials of medical devices inEngland, Wales and Northern Ireland the provi-sions for inclusion of incapacitated adults are laiddown in the Medicines for Human Use (ClinicalTrials) Regulations 2004 and as amended In Scot-land, these regulations and also the Adults withIncapacity (Scotland) Act 2004 (regulations 4 to

ar-16 and Parts 3 and 5 of Schedule 1) will also ply Such requirements are considered suitable forother types of clinical research

ap-When considering a patient who is unable toconsent for themselves for suitability for a trial, thedecision on whether to consent to, or refuse, par-

ticipation in a trial will be taken by a legal

repre-sentative who is independent of the research team

and should act on the basis of the person’s sumed wishes The type and hierarchy of legalrepresentative who should be approached to giveinformed consent on behalf of an incapacitatedadult prior to inclusion of the subject in the trial

pre-is given in Table 14.1 (note that arrangements forScotland are slightly different)

Table 14.1 Type and hierarchy of legal representative who can give informed consent on behalf of an incapacitated adult prior to inclusion of the subject in the trial.

England, Wales and Northern Ireland Scotland

A person not connected with the conduct of the trial who is:

(a) suitable to act as the legal representative by virtue of

their relationship with the adult, and

(b) available and willing to do so

1A Any guardian or welfare attorney who has power toconsent to the adult’s participation in research

1B If there is no such person, the adult’s nearest relative

as defined in section 87(1) of the Adults with Incapacity(Scotland) Act 2000

A person not connected with the conduct of the trial who is:

(a) the doctor primarily responsible for the adult’s medical

treatment, or

(b) a person nominated by the relevant health care provider

(e.g an acute NHS Trust or Health Board)

A professional legal representative may be approached if

no suitable personal legal representative is available

A person not connected with the conduct of the trial who is:(a) the doctor primarily responsible for the adult’s medicaltreatment, or

(b) a person nominated by the relevant health care provider

A professional legal representative may be approached if it

is not reasonably practicable to contact either 1A or 1Bbefore the decision to enter the adult into the trial is made.Informed consent must be given before the subject isentered into the trial

Audit, research ethics and research governance 125

The appropriate legal representative should be

provided with an approved Legal Representative

Information Sheet and Legal Representative

In-formed Consent Form to document the consent

process

The consent given by the legal representative

re-mains valid in law even if the patient recovers

ca-pacity However, at this point, the patient should

be informed about the trial and asked to decide

whether or not they should continue in the trial,

and consent to continue should be sought

Research governance

Research governancecan be defined as the broad

range of regulations, principles and standards of

good practice that exist to achieve, and

continu-ously improve, research quality across all aspects

of health care in the UK and worldwide In the UK,

the Department of Health published the first

Re-search Governance Framework for Health and

So-cial Care in 2001, and this was updated in 2005 and

sets out to:

r safeguard participants in research;

r protect researchers/investigators (by providing

a clear framework to work within);

r enhance ethical and scientific quality;

r minimise risk;

r monitor practice and performance;

r promote good practice and ensure lessons are

learned

Research governance includes research that is

concerned with the protection and promotion of

public health, undertaken in or by the Department

of Health, its non-Departmental Public Bodies and

the NHS, or within social care agencies It includes

clinical and nonclinical research; and any research

undertaken by industry, charities, research

coun-cils and universities within the health and social

care systems Everyone who undertakes

health-care research (research involving individuals, their

tissue or their data) therefore has responsibilities

for research governance This includes lead

re-searchers, research nurses, students undertaking

research, as well as NHS organisations where

re-search takes place and universities who may

em-ploy or supervise researchers or act as sponsor

or-ganisations

Research governance should be considered atall stages of the research, from the initial develop-ment and design of the research project, throughit’s set-up, conduct, analysis and reporting Re-searchers need to ensure that:

r day to day responsibility for elements of eachresearch project is clearly stated;

r research follows the agreed protocol;

r research participants receive the appropriatecare while participating in the research;

r data protection, integrity and confidentiality ofall records is intact;

r reporting adverse incidents or suspected conduct is undertaken

mis-Research governance approval is required fromany NHS Trust before the research can take place

on their premises, or access patients, their sue or their data All research documents such asresearch protocol, participant information sheetsand informed consent forms, details of NHS Re-search Ethics Committee approval, researcher CVare submitted for governance checks Current sys-tems for multi-centre research review the researchgovernance compliance at a nominated lead NHSTrust, and local information only is submitted tothe local NHS Trusts The Integrated Research Ap-plication System (www.myresearchproject.org.uk)

tis-is used for submtis-ission of research information toNHS Research Ethics Committees as well as NHSresearch governance approval

KEY LEARNING POINTS

r Audit is a process to ensure that delivery of

health care meets accepted standards of care and can identify both exemplars of very good or very poor practice

r To complete the audit cycle, one must demonstrate that any identified deficiencies have been acted upon and there has been improvement

r All research has ethical implications but these

tend to be more serious with RCTs than observational studies especially around the issue of clinical equipoise RCTs may also use sham procedures to maintain blinding

r In general terms, it is essential to avoid any

unnecessary harm to participants, ensure they

are fully informed prior to consent and maintain

participant confidentiality

r Studies of children need to seek child assent as

well as parental consent

r Special rules apply to research with

incapacitated adults where is needs to be shown

that the research could not be done in any other

way and is in the participants’ best interest

r Research ethics committees must approve

research studies before they commence and

there are often governance procedures that

ensure that the research is undertaken to the

highest level.

REFERENCES

Barter PJ, Caulfield M, Eriksson M, et al (2007)

Ef-fects of Torcetrapib in patients at high risk for

coronary events NEJM 357: 2109–22.

Hodsman A, Ben-Shlomo Y, Roderick P, et al.

(2011) The ‘centre effect’ in nephrology: what do

differences between nephrology centres tell us

about clinical performance in patient

manage-ment? Nephron Clin Pract 119: c10–c17.

Olanow CW, Goetz CG, Kordower JH, et al (2003) A

double-blind controlled trial of bilateral fetal

ni-gral transplantation in Parkinson’s disease Ann

Neurol 54: 403–14.

Vernooij MW, Ikram MA, Tanghe HL, et al (2007)

Incidental findings on brain MRI in the general

population N Engl J Med 357: 1821–8.

FURTHER READING

Bristol Royal Infirmary Inquiry (2001)

Learn-ing from Bristol: the report of the public quiry into children’s heart surgery at the Bristol Royal Infirmary 1984–1995 Norwich: Stationery

in-Office, (CM 5207.) Available at inquiry.org.uk/

www.bristol-Campbell A, Jones G, Gillett G (2001) Medical

Ethics, 3rd edn Oxford: Oxford University Press.

Hope T, Savulescu J, Hendrick J (2008) Medical

Ethics and Law: The Core Curriculum, 2nd

re-vised edn London: Churchill Livingstone

Murphy, Timothy (2004) Case Studies in

Biomedi-cal Research Ethics Cambridge, MA: MIT Press.

UK National Research Ethics Service website:http://www.nres.npsa.nhs.uk/

Audit, research ethics and research governance 127

Appendix 14.1 Differentiating research, service evaluation and clinical audit

The attempt to derive generalisable new

knowledge including studies that aim to

generate hypotheses as well as studies that

aim to test them

Designed and conducted solely todefine or judge current care

Designed and conducted toproduce information to informdelivery of best care

Quantitative research – designed to test a

hypothesis

Qualitative research – identifies/ explores

themes following established methodology

Measures against a standard

Quantitative research – may involve

evaluating or comparing interventions,

particularly new ones

Qualitative research – usually involves

studying how interventions and relationships

are experienced

Involves an intervention in use only

The choice of treatment is that ofthe clinician and patient according

to guidance, professionalstandards and/or patientpreference

Involves an intervention in use only.The choice of treatment is that ofthe clinician and patient according

to guidance, professionalstandards and/or patientpreference

Usually involves collecting data that are

additional to those for routine care but may

include data collected routinely May involve

treatments, samples or investigations

additional to routine care

Usually involves analysis of existingdata but may include administration

of interview or questionnaire

Usually involves analysis of existingdata but may include administration

of simple interview or questionnaire

Quantitative research – study design may

involve allocating patients to intervention

groups

Qualitative research – uses a clearly defined

sampling framework underpinned by

conceptual or theoretical justifications

No allocation to intervention: thehealth professional and patienthave chosen intervention beforeservice evaluation

No allocation to intervention: thehealth professional and patienthave chosen intervention beforeaudit

Normally requires REC review Refer to

www.nres.npsa.nhs.uk/applications/apply/

for more information

Does not require REC review Does not require REC review

∗Service development and quality improvement may fall into this category

Source: adapted from Defining Research: NRES guidance to help you decide if your project requires review by a Research Ethics Committee, NHS National Patient Safety Agency 2010.

questions – Part 2:

Evidence-based medicine

Q1 Do tired doctors make more medical errors?

(modified from Landrigan et al., N Engl J Med

2004)

Newly qualified doctors (PRHOs) typically

work the greatest number of hours per week

which may mean that they are especially

prone to fatigue related errors Whilst there is

evidence that sleep deprivation impairs

neu-robehavioural performance, it is still unclear

whether there is an increased risk of medical

errors

The Intern Sleep and Patient Safety Study

was conducted in the medical intensive care

unit and coronary care unit of a large

aca-demic hospital in Boston PRHOs between

July 2002 and June 2003 were allocated to

work either the traditional schedule (work

week average of 77 to 81 hours with up to 34

continuous hours of scheduled work, when

clinic occurred after they were on call) or

the intervention schedule (maximal

sched-uled hours 60–63 per week, with

consecu-tive hours of work limited to approximately

16 hours) The allocation was done by the

research team using random numbers and

none of the team had any prior knowledge of

the PRHOs’ past academic record or clinical

performance During any week, all PRHOs on

each unit were working the same schedule

The aim of the intervention schedule was to

improve opportunities for sleep while

min-imising errors The primary outcome of the

study was the number of serious medical

er-rors in which PRHOs were directly involved,

this was recorded through direct observation

by physicians Blinding of these physician

observers was not possible as they had to dertake the same work patterns

un-During the study there were 634 sions in total The patients’ and PRHOs’ char-acteristics were very similar within the twoschedules All the PRHOs who were ran-domised completed the study except for onedoctor allocated to the traditional schedulewho dropped out due to ill-health TableQB.1 presents the rates of serious errors andpreventable adverse events per 1000 patient-days within each schedule

admis-(a) What is the null hypothesis?

(b) Does the table provide any evidence

of an association between the type ofschedule and the rate of ‘serious medicalerrors’? Comment on the rate ratio, con-fidence interval, and P value

(c) What type of errors does the interventionschedule most effectively reduce? Justifyyour answer

(d) Why was it important that the researcherwho decided whether a PRHO was allo-cated to either the intervention or tradi-tional schedule had no knowledge aboutthe PRHO? What do we call the designprocedure employed in this type of study

to prevent this potential bias? If this doesnot occur how could the results havebeen biased

(e) What is meant by ‘blinding’ and did it cur in this study? If a study is unblindedwhat might occur? How could this haveaffected the results in this study?(f ) What other type of bias may effect thistype of study design? Did it occur in thisspecific study?

oc-Epidemiology, Evidence-based Medicine and Public Health Lecture Notes, Sixth Edition Yoav Ben-Shlomo, Sara T Brookes and Matthew Hickman.



Self-assessment questions – Part 2: Evidence-based medicine 129

Table QB.1 Incidence of serious medical errors.

Rate per 1000 patient-days Intervention

schedule

Traditional schedule Rate ratio∗ 95% confidence interval P value

∗Rate ratio can be interpreted similarly to the risk ratio

# Injury due to a non-intercepted serious error in medical management

(g) In addition to the potential biases

men-tioned in questions d–f, what other

ex-planations should be considered before

concluding that the intervention

sched-ule reduces the rate of serious errors?

How likely are each of these?

(h) Assuming the association between work

schedule and serious errors is true, why

is it important to look at the association

between work schedule and preventable

adverse events before any policy changes

are made What else should also be

considered?

(i) Does the intervention schedule lead to

fewer preventable adverse events? Please

comment on the rate ratio, confidence

interval and P value? How precise is the

estimate of the rate ratio?

(j) How generalisable are the findings?

Would you suggest implementation of

the intervention schedule into the UK?

Q2 Blinding in RCTs

For each of the following trial designs, state

whether it is possible to blind patients

and/or researchers to the allocation of

treatments

(a) A drug trial of a new antidepressant

com-pared to placebo where the outcome

measure is a patient rated depression

scale

(b) Group versus individual speech

ther-apy sessions for patients who have a

language difficulty (dysphasia) after a

stroke where the outcome measure is

a recorded conversation reading aspecific piece of text

(c) A hyptertensive trial where patients aregiven a drug (beta-blocker) that alsoslows down heart rate or an identicallooking placebo and a nurse measuresthe blood pressure

(d) A RCT of two different joint prosthesesfor osteoarthritis of the hip with the out-come measure being hip flexion withoutpain done by the researcher and a pa-tient administered quality of life score.(e) A trial of acupuncture for arthriticpain using a patient completed painindex and participants who have neverpreviously had acupuncture

Q3 Economic evaluation

The economic evaluation was conducted

as part of a randomised controlled trialwhich examined the effectiveness, accept-ability and accessibility of a general practi-tioner with special interest (GPSI) dermatol-ogy service compared with routine hospitaloutpatient care Patients who were referred

to a hospital outpatient dermatology clinicand were deemed suitable to be managed

by a general practitioner with special est were randomised to either usual care (i.e.hospital outpatient care) or the GPSI service.Resources were measured for the patientsfor nine months following randomisation.Most of the NHS resources were measuredthrough computerised systems Resourcesused by patients and their companions,and information on time off work (lost

inter-production) were measured through patient

self completed postal questionnaires

Two types of evaluation using differing

perspectives were conducted

(I) A primary outcome measure, the

derma-tology life quality index score, and costs

were evaluated from an NHS perspective

(II) This outcome measure and others (an

ac-cess score, patient satisfaction with the

consultation, satisfaction with facilities,

attendance rates, and waiting times) and

costs were evaluated from several

per-spectives (NHS, patient and companion,

societal lost production)

A sensitivity analysis was conducted which

extended the collection of NHS resources for

an additional 3 months (12 months in total)

(Based on Coast J, Noble S, Noble A, Horrocks

S, Asim O, Peters TJ, Salisbury C (2005) BMJ

331(7530): 1444–8.)

(a) Identify the types of resource use that

you would collect if the evaluation was

from

i an NHS/health service provider

per-spective

ii societal perspective

(b) What are the potential problems with

using self-completed questionnaires to

measure patient costs and time off work?

(c) A cost-effectiveness analysis could be

used for the first type of evaluation What

is thePICOfor this analysis?

(d) What type of economic evaluation might

you use for the second type of

evalua-tion?

(e) Thecost-effectiveness analysiswill give

evidence as to which is the most

tech-nically efficientprovision of care If this

evaluation was to aid the creation of

an allocatively efficient health care

sys-tem what outcome measure(s) should

be used

(f ) Comparing the new GPSI service with

routine outpatient care, the results

from the first type of evaluation were

in the North East quadrant of the

cost-effectiveness plane What does this

mean?

(g) How should uncertainty in relation to

thecost-effectiveness analysisbe

repre-sented?

(h) Why do you think thesensitivity

analy-siswas conducted?

Q4 Diagnostic tests

(a) The abstract of a recent publicationhas reported the following performancemeasures for a new diagnostic test: sen-sitivity 50%, specificity 98%, positive pre-dictive value 86%, negative predictivevalue 89%

i What percentage of patients with thedisease are correctly identified by thetest?

ii Given a positive test result, what is therisk of having the disease ?

iii What is the false positive rate of thistest?

iv What percentage of patients with anegative test will still have the disease?

v Is this test more useful for ruling out orruling in the diagnosis?

(b) When assessing a new diagnostic test:

i It should have a high specificity(>90%) if it is important not to miss

new cases of disease True or false?

ii If it is more expensive than existingtests it should not be introduced True

or false?

iii If subsequent investigation of peoplewho test positive is invasive and risky,then the test should have a high posi-tive predictive value True or false?

iv Cohort studies are the best study sign to evaluate whether a new diag-nostic test improves health True orfalse?

de-v The best diagnostic test has 100% sitivity and 100% specificity True orfalse?

sen-Q5 Prognosis

State which of the following questions aretrue about prognosis (T) and which are not(F):

(a) A 2-year-old girl has glue ear Is she likely

to have long-term hearing impairment?(b) A 60-year-old man has just been di-agnosed with lung cancer What is hischance of surviving 10 years?

(c) A 9-year-old boy has symptoms of tonia (neurological movement disorder).What is the most likely cause?

dys-(d) An injecting drug user (female, 30 yearsold) has just been diagnosed with hep-atitis C How likely is she to develop livercancer?

Self-assessment questions – Part 2: Evidence-based medicine 131

(e) A nursery-age child is diagnosed with

measles Is he likely to pass this on to

unvaccinated family members through

household contact?

Q6 Systematic reviews

The figure shows the results from a Cochrane

systematic review of randomised controlled

trials of exercise-based rehabilitation for

people with coronary heart disease The

ma-jority of patients randomised had suffered

an acute myocardial infarction and were

middle-aged men The following questions

refer to this systematic review

Review Exercise-based rehabilitation for coronary heart disease

01 Exercise only versus usual care

01 Total Mortality

Treatment n/N

Control n/N

Relative risk (fixed) 95% CI

Relative risk (fixed) 95% CI Weight (%)

Test for heterogeneity chi-square = 10.50 df = 11 p = 0.4858

Test for overall effect = –2.08 p = 0.04

3/42 12/116 21/152 0/40 1/35 8/146 24/328 2/84 13/131 1/29 2/25 35/157

2.5 9.6 16.9 0.4 0.8 6.6 19.3 1.7 10.3 1.4 2.0 28.4

1.22 [0.29, 5.12] 1.37 [0.68, 2.76] 0.58 [0.29, 1.13] 9.00 [0.50, 161.87] 1.03 [0.07, 15.81] 0.60 [0.20, 1.79] 0.63 [0.34, 1.19] 1.43 [0.25, 8.36] 0.40 [0.15, 1.10] 0.23 [0.01, 5.52] 0.20 [0.01, 3.97] 0.79 [0.51, 1.24]

Which of the following statements aretrue/false?

(a) The results are presented as a field plot(b) Whether treatment increased or de-creased mortality is shown in the figure(c) The pooled effect shows that exercise-based cardiac rehabilitation is betterthan usual care

(d) The trials with the longest bars are thebiggest

(e) The size of the square for each trial resents the precision of the estimate

rep-Part 3

Public health

In this chapter you will learn:

✓ to define public health and distinguish between public health and individual health care;

✓ to identify how public health is measured or diagnosed;

✓ to identify types of public health intervention.

Introduction

Public health has been defined as: ‘the science

and art of preventing disease, prolonging life, and

promoting health through organised efforts of

so-ciety’ Public health focuses on improving the

health of entire populations rather than on

individ-ual patients The population is the patient Tools

for improving population health range from the

development of new clinical services for treating

disease, screening programmes to detect disease

at an early (treatable) stage, immunisation to

pre-vent the transmission of infectious diseases, to

leg-islation to prohibit actions or behaviours, or health

improvement in schools and workplaces Public

health aims to encompass the whole clinical

ice-berg (see Figure 15.1)

Public health seeks to target all ill health

com-prising the population that are asymptomatic or

prodromal (unaware of illness), the populationthat have not yet presented to medical services aswell as population being managed by health careservices

Public health practice

Public health is an interdisciplinary practice –with public health specialists operating locally, na-tionally and internationally; within healthcare ser-vices, local authorities, the voluntary sector andother government bodies – and drawing on a mul-titude of skills As we write this chapter UK pub-lic health along with the NHS is being reorgan-ised This is not new – and however public health

is organised the type of problems specialists tackleand the approach they take will be similar What iscommon and critical is the population approach,i.e that health needs are identified and assessedand interventions delivered and evaluated at apopulation level

Epidemiology, Evidence-based Medicine and Public Health Lecture Notes, Sixth Edition Yoav Ben-Shlomo, Sara T Brookes and Matthew Hickman.



Known tomedical services

Aware of illness but notsought adviceDiseased but not yetaware of illnessWell

The three domains of public health in the UK

are:

Health

improvement

Improving services

Health protection

Inequalities Clinical

effectiveness

Infectiousdiseases

poisons

evaluation

EmergencyresponseFamily/community Clinical

governance

Environmentalhealth hazards

Surveillance and

monitoring of

specific diseases

and risk factors

Many of these are covered elsewhere in the

book – including infectious disease

epidemiol-ogy and health protection; and evidence based

medicine which underpins improving services.

The issues in health improvement emphasise that

public health aims to reduce inequalities as well as

improve population health and that public health

interventions can operate at multiple levels As

well as the domains above, public health is

con-cerned with Health Impact Assessment (HIA) –

UK and international examples of which are

col-lated at the HIA Gateway HIA is defined by WHO

as ‘A combination of procedures, methods and

tools by which a policy, programme or project may

be judged as to its potential effects on the health of

a population, and the distribution of those effects

within the population’

The United States Communicable Disease trol has identified ten public health achievements

Con-of the twentieth century (Figure 15.2)

It is estimated that the average lifespan in the

US increased by>30 years during the twentieth

century and that 25 years (∼3/4) of the gain isattributable to public health Similar gains haveoccurred in other industrial/developed countries.The contribution of public health interventions in-clude: eradication of smallpox, elimination of po-lio, and control of many other infections through

‘vaccination’; reductions in motor vehicle dents due to improvements in driving and ‘motor-vehicle safety’; reductions in environmental ex-posure and occupational injury through ensuring

acci-‘safer work places’; improved sanitation, ity of clean water, and antimicrobials leading tobetter ‘control of infectious diseases’; reductions

availabil-in risk behaviours, such as smokavailabil-ing, and control

of blood pressure and early detection have tributed to a decline in ‘deaths from coronaryheart disease and stroke’; better hygiene and nutri-tion of mothers and babies has contributed to re-ductions in neonatal and maternal mortality; andthe many anti-smoking campaigns and policieshave led to changes in public perceptions of thedangers and acceptability of smoking by the pub-lic and substantial reductions in smoking and en-vironmental exposure to tobacco in the popula-tion Morbidity and socioeconomic circumstancesalso have improved through ‘safer and healthierfoods’ reducing frequency of diseases associatedwith nutritional deficiency (such as rickets andpellagra); family planning/contraceptive servicesreducing family size and transmission of sexu-ally transmitted infections; and fluoridation hasmade substantial reductions in tooth decay andloss

4 Control of infectious diseases

5 Decline in deaths from coronary heart disease and stroke

6 Safer and healthier foods

7 Healthier mothers and babies

8 Family planning

9 Fluoridation of drinking water

10 Recognition of tobacco use as a health hazard

Source: http://www.cdc.gov.

These represent a range of different

interven-tions:

r primary prevention: such as vaccination and

health promotion campaigns; legislation and

enforcement to promote safer driving, and safer

work places;

r environmental and social changes: including

improved nutrition and availability of clean

wa-ter and fluoridated wawa-ter;

r medical advances: such as hygiene during child

birth and other surgical interventions; and

more aggressive identification and treatment of

early signs of heart disease

The health problems affecting low and middle

income countries differ from those of

industri-alised nations – and some of the public health

achievements of the twentieth century

identi-fied above are as yet unresolved in developing

countries For example, there were approximately

6.5 million deaths in children under five in

African and Southeast Asian countries in 2008

(Black et al., 2010) The top six causes were:

pneumonia (18%); diarrhoea (15%); neonatal birthcomplications (12%); neonatal asphyxia (9%) orsepsis (6%) and malaria (8%) Key interventions

to prevent these deaths include: clean/sterile livery, nutrition and nutritional deficiencies (e.g.vitamin A and zinc), antibiotics, water sanitation,vaccination (Hib and measles), oral rehydration,and mosquito (insecticide treated) nets Key pub-lic health interventions in developed and develop-ing countries can be medical, educational, social

de-or legal

Public health diagnosis

The steps to improving public health are gous to clinical medicine but with slightly differenttools We need to ‘diagnose’ the problem The tools

analo-at our disposal are informanalo-ation on the populanalo-ation,routine data on mortality and morbidity, hospi-talisation, public health surveillance data, popu-lation health surveys and other epidemiologicalstudies Some of the key sources used in the UK

are listed below These allow us to measure rates of

disease in the population, and consider variations

in health and disease in different populations and

(6) notification data: infectious disease (e.g.

meningitis, mumps), congenital

malforma-tions, maternal deaths;

(7) laboratory reporting statistics (e.g sentinel

surveillance and other routine information

on laboratory tests and diagnoses);

(8) morbidity surveys: National Psychiatric

Mor-bidity Survey; Health Survey for England (to

give prevalence of e.g CVD, asthma);

(9) lifestyle surveys: General Health Survey,

Health Survey for England (prevalence of

smoking, obesity alcohol, exercise etc.);

(10) qualitative and quantitative research studies.

(11) national confidential enquiries – e.g

mater-nal mortality, peri-operative deaths and

sui-cide and homisui-cide by people in contact with

mental health services

In England analysis of these data sources are

routinely undertaken at a local level and published

as aJoint Strategic Needs Assessment, to inform

commissioning of NHS and local authority

ser-vices, and in an annual independent report of the

Director of Public Health Importantly these tools

also allow public health specialists to address

spe-cific questions such as:

r Is the CHD death rate in a local populationhigher than the regional or national average,and are the rates re-vascularisation higher orlower than expected?

r Do increases in cannabis exposure cause creases in schizophrenia?

in-r Is breast cancer survival in Britain improvingcompared to other European countries?

r What causes Sudden Infant Death Syndrome(cot death) and how can we prevent it?

r Is childhood obesity increasing?

r Has Chlamydia screening reduced the dence of pelvic inflammatory disease?

inci-r What strategies could be used to prevent cide?

sui-and many more

These questions can be reformulated as a PICO

as discussed earlier – the difference is that we aremeasuring the intervention and the outcome at apopulation level

Public health interventions

After making our diagnosis we need to prescribe

an intervention or select a management that canaddress the health problem This will involve acritical appraisal of the evidence on effectiveness

of alternative interventions in the same way asevidence-based medicine is recommended forclinical practice For example, from 1995 to 2005the proportion of children (aged 2–15) classified asobese increased from 11% to 18% (establishing theneed for public health action) ACochrane review

of primary prevention studies suggested that themajority did not demonstrate strong evidence andthat many studies were limited in design, duration

or analysis; but that perhaps comprehensivestrategies which address diet and physical activity,change the environment, and involve psychoso-cial support have the best change of preventingobesity (Summerbell, 2005) Strategies adopted

by local governments and health trusts, therefore,have tended to be multifaceted

Unlike clinical medicine the implementation ordelivery of the intervention may require the de-velopment of health strategies, mobilisation of re-sources and introduction of new services and per-suasion of other government partners to adapt

or change their policies (as highlighted below)

Public health 139

Improving population health can involve

restrict-ing individual freedom Since public health

inter-ventions and strategies operate at a population

level; they may create a tension between

individ-ual choices and the public health For example,

lo-cal residents launched a legal challenge through

a judicial review of the decision in South England

by South Central Strategic Health Authority to add

fluoride to the local water supply

Cigarette smoking, heavy drinking and obesity

are related to multiple causes of death and cause

substantial premature mortality in UK For

in-stance:

r Smoking is related to over 40 causes of death

and morbidity, and causes approximately

100,000 deaths per year are due to smoking

including a third of persistent smokers

r Alcohol abuse and misuse is associated with

over 50 causes of death and morbidity, with

esti-mates of direct and indirect causes of mortality

annually ranging from 20 000 to 70 000 deathsper year; population levels of drinking in the UKhave increased in the last 20 years consistentwith increases in the number of people dyingfrom liver disease (one of the few major causes

of death which is increasing and the mean age

of diagnosis and death is decreasing)

r By 2008 approximately 1 in 4 men and womenwere obese, a twofold and 150% increase re-spectively Obesity is associated with Type 2 dia-betes, osteoarthritis, coronary heart disease andsome cancers, and will add substantially to therisk of death and disability if present with smok-ing and alcohol misuse

Interventions to reduce these behaviours haveadopted a range of methods and styles TheNuffield School on Bioethics classified a Public Health Intervention Ladderin the degree of socialcontrol on individual choice (see Table 15.1)

Table 15.1 Public Health Intervention Ladder

Eliminate choice: Introduce laws that

entirely eliminate choice

Seatbelt legislation, drink drive laws, bans on alcohol sales in thoseunder 18

Restrict choice Introduce laws that restrict

the options available to people

Banning smoking in public places; banning transfatty acids as aningredient of processed food in restaurants∗; banning ‘happy hours’and reducing drinking hours∗

Guide choice through disincentives.

Introduce financial or other disincentives to

influence people’s behaviour

Increasing taxes on cigarettes; introducing a minimum price per unit

of alcohol∗

Guide choices through incentives.

Introduce financial or other incentives to

influence people’s behaviours

Offering tax-breaks on buying bicycles for travelling to work;subsidising gym membership; contingency management(interventions in which substance misusing people receive tangible,positive reinforcers for objective evidence of behaviour change) aspart of the treatment of people with alcohol, smoking, or weightproblems

Guide choices through changing the

default policy.

Changing the standard side dish in school meals from chips to ahealthier alternative; changing nature of drinking environments sothat alcohol served with food∗)

Enable choice Help individuals to change

their behaviours

Providing free ‘smoking cessation’ programmes; exerciseprescription; provide brief interventions for alcohol, or smoking ingeneral practice, A&E and other health and social settings

Provide information Inform and educate

the public

Campaigns to encourage people to walk more or eat five portions offruit and vegetables a day; food labelling to identify health andunhealthy foods∗; smoking warnings on cigarette packs; information

on recommended drinking levels and units of alcohol

Do nothing or simply monitor the

current situation

Several of the suggestions above∗have yet to be introduced;monitor trends in alcohol harm, such as emergency and inpatientadmissions and assaults http://www.nwph.net/alcohol)

Note: Several of the interventions suggested marked as (∗) have yet to be introduced;

Public health action

We examine two further examples of public health

analysis and intervention: on prevention of suicide

and sudden infant death syndrome (SIDS)

Suicide Prevention

Suicide is an important cause of premature

mor-tality, especially among young people, and is the

most severe outcome of mental illness For

exam-ple, each year during the 1990s in the UK there

were approximately:

r 4,500 deaths from suicide;

r >200,000 hospital attendances for self-harm;

r 1 million individuals experience suicidal

thoughts;

r 2 million people prescribed an antidepressant;

r 5 million adults with neurotic symptoms;

r 150 million working days lost through mentalillness;

Suicide is a complex public health problem, (asshown in Figure 15.3)

There are multiple potential influences andcauses of suicide Another way of looking at sui-cide and injury prevention is to construct aHad- don Matrix(Haddon, 1999) which describes riskand protective factors in terms of the person, agent

or event, and environment and whether they cur before, during or after the injury We will fo-cus on one potential source of prevention – themethod of suicide – and show how the ‘restriction’

oc-or ‘elimination’ of choice’ can reduce the all number of suicides The figures show that formen and women the rate of suicide by domes-tic gas fell as coal gas which had high carbonmonoxide (CO) content and was highly toxic was

over-IMPULSIVEBEHAVIOUR INRESPONSE TOLIFE EVENTS

• Personal & cultural acceptability

(may influence some,

but not all, domains

in this figure)

ENVIRONMENTAL

INFLUENCES ON

NEURODEVELOPMENT

e.g childhood abuse;

loss of parent; low

birthweight

MENTAL ILLNESSdepression;

schizophrenia

SUICIDALTHOUGHTS

ATTEMPTED

AVAILABILITY OFEFFECTIVETREATMENTS/ANTIDOTES

• Motherhood

• Social support

• Help seeking

• Religious sanctions against suicide

PROTECTIVEFACTORS

CHOICE OF METHOD/METHOD AVAILABILITY(media, culture)

Source: After Gunnell D, Lewis G (2005) Studying suicide from the lifecourse perspective: implications for prevention Br J

Psychiatry 187: 206–8 With permission from The Royal College of Psychiatrists.

All othermethods

Total

Domestic gas

All othermethods

Domestic gas

1955–1971

Source: after Kreitman N (1976) The coal gas story: United Kingdom suicide rates, 1960–71 Brit J Prev Soc Med

30: 86–93, with permission from BMJ Publishing Group Ltd.

gradually replaced by natural gas (low CO), until

by 1970s there was no domestic supply based on

coal gas and no suicides from this method What

is remarkable – and critical to suicide prevention –

is that the reduction in deaths from domestic gas

have not been replaced by other methods In the

1950s and early 1960s coal gas was the

common-est method of suicide; its withdrawal and eventual

removal led to approximately 9,000 fewer suicides

(Figure 15.4)

This observation has led to interest in

control-ling other methods of suicide For example, the

introduction of legislation restricting the

quan-tity of paracetamol that could be bought over

the counter is associated with a reduction in

sui-cide deaths due to paracetomol as well as

de-clines in liver transplants More recent bans on

coproxamol also are estimated to have prevented

around 150–250 poisoning deaths per year in the

UK These interventions and evaluations of

im-pact are derived from the examination of routine

data sets and an assessment of the natural

his-tory and causal influences on disease Worldwide

the commonest method of suicide is pesticide

self-poisoning – accounting for over 250,000 deaths per

year – bans on the most toxic pesticides may have

a profound impact on the incidence of suicideworldwide

SIDS prevention

Sudden Infant Death Syndrome (SIDS) or ‘cotdeath’ was responsible for approximately 900deaths per year (1 in 500 children in the first year

of life) in UK in the 1970s/1980s, with marked sonal variation peaking in winter months Someresearchers thought it was possible that infantssleeping position (prone – lying on stomach vs.supine – lying on back) may influence risk Ad-vice on the sleeping position of babies was largelyunchanged since the 1940s when the most pop-ular child-rearing book suggested that babiesshould be encouraged to sleep on their stomach,i.e a prone sleeping position – as illustrated inFigure 15.5

sea-A case control study examining potential causes

of SIDS with 72 cases and 144 controls found the

following (Fleming et al., 1990, p 85):

r Odds Ratio (OR) of prone sleeping: 8.8 (95% CI7.0–11.0; p< 0.001);